Process for producing alkoxyiminoacetamide compounds

Abstract: There is disclosed a process for producing an alkoxyiminoacetamide compound which is useful as agricultural fungicides. Also dislclosed are novel intermediate compounds for the above process and their production.

Description: The present invention relates to the production of alkoxyiminoacetamide compounds, particularly to an industrial process for producing alkoxyiminoacetamide compounds useful as agricultural fungicides. EP-A-0 477 631 and EP-A-0 432 503 disclose certain processes for producing fungicides of the type with which the present invention is concerned; however, neither of these publications teach the beneficial effect of the slow addition over a considerable period of time of the halogenating agent which is reacted with compound (III) as described below. Also these publications are not concerned with increasing the E-isomer content by isomerisation under acidic conditions. Hitherto, the present inventors have studied to develop agricultural fungicides for many years. As a result, it has been found that alkoxyiminoacetamide compounds of the formula (I): wherein A is hydrogen, lower alkyl, lower alkenyl, lower alkynyl, lower alkoxy, cyclo(lower)alkyl, cyclo(lower)alkenyl, optionally substituted phenyl or an optionally substituted heterocyclic group; B is -CH 2 -, -O-, -S-,-CH(OH)-, -CO-, -NR 3 - (wherein R 3 is hydrogen or lower alkyl), -CH 2 CH 2 -, -CH=CH-, -C≡C-, -CH 2 O-, -CH 2 S-, -CH 2 S(O)-, -OCH 2 -, -SCH 2 -, -S(O)CH 2 - or epoxy; R is lower alkyl; R 1 and R 2 are each independently hydrogen or lower alkyl; and the bond ∼ represents any configuration of the E-isomer, Z-isomer or a mixture of the E- and Z-isomers; exhibit potent controlling activity against wide varieties of pathogens of plants and cause little damage to useful plants such as grains, vegetables, fruits and the like (see U.S. Patent No. 5185342 and JP-A 4-182461). The characteristic of the chemical structure of the alkoxyiminoacetamide compound (I) is that the carboxyl group of the acetic acid moiety at the o-position of the benzene ring is converted into an optionally substituted carbamoyl group and that an alkoxyimino group is introduced to the α-position. Based on these characteristics, the compound (I) generally exhibits more excellent fungicidal activity than that of a corresponding alkyl alkoxyiminoacetate wherein the carboxyl group of the carboxylic acid moiety is converted into an alkoxycarbonyl group. The alkoxyiminoacetamide compound (I) exists as the E- or Z-isomer. In general, the E-isomer has superior fungicidal activity to that of the Z-isomer. The object of the present invention is to provide an industrially useful process for producing alkoxyiminoacetamide compounds, particularly a process for producing E-isomers of alkoxyiminoacetamide compounds in high purity. As described above, the present inventors have found that the alkoxyiminoacetamide compounds of the formula (I), particularly their E-isomers, have high utility as agricultural fungicides. Based on this finding, they have studied an industrial process for producing the compounds. As a result, the present invention has been completed. That is, the present invention provides: A process for producing an alkoxyiminoacetamide compound of the formula (I): wherein A is hydrogen, C 1 -C 8 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, C 1 -C 8 alkoxy, cyclo(C 3 -C 8 )alkyl, cyclo(C 3 -C 8 )-alkenyl, optionally substituted phenyl or an optionally substituted heterocyclic group; B is -CH 2 -, -O-, -S-, -CH(OH)-, -CO-, -NR 3 - (wherein R 3 is hydrogen or C 1 -C 8 alkyl),-CH 2 CH 2 -,-CH=CH-, -C≡C-, -CH 2 O-, -CH 2 S-, -CH 2 S(O) -, -OCH 2 -, -SCH 2 -, -S(O)CH 2 - or epoxy; R is C 1 -C 8 alkyl; and R 1 and R 2 are each independently hydrogen or C 1 -C 8 alkyl; which process comprises halogenating a compound of the formula (III): wherein the bond ∼ represents any configuration of the E-isomer, Z-isomer or a mixture of the E- and Z-isomers and the other symbols are as defined above, to obtain a compound of the formula (IV): wherein X is halogen and the other symbols are as defined above; reacting the compound of the formula (IV) with an amine of the formula: HNR 1 R 2 (wherein R 1 and R 2 are as defined above) ; and treating the resulting compound with an acid for isomerisation to increase the E-isomer content, wherein said halogenation is carried out by the addition of a halogenating agent to said compound of formula III over a period of time between 5 and 24 hours. By the term "lower" used in the definitions of the formulas is meant having not more than 8 carbon atoms, preferably not more than 6 carbon atoms, more preferably not more than 4 carbon atoms unless otherwise indicated. Examples of the lower alkyl represented by R, R 1 , R 2 , R 3 and A include alkyl having 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl. Examples of the lower alkenyl represented by A include alkenyl having 2 to 8 carbon atoms, preferably 3 to 6 carbon atoms, for example, allyl, propenyl, isopropenyl, butenyl, isobutenyl, pentenyl, hexenyl, hexadienyl. Examples of the lower alkynyl represented by A include alkynyl having 2 to 6 carbon atoms, preferably 2 to 4 carbon atoms, for example, propargyl, ethynyl, butynyl. Examples of the lower alkoxy represented by A include alkoxy having 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, s-butoxy, t-butoxy. Examples of the cyclo(lower)alkyl represented by A include cycloalkyl having 3 to 8 carbon atoms, preferably 3 to 6 carbon atoms, for example, cyclopropyl, cyclopentyl, cyclohexyl. Examples of the cyclo(lower)alkenyl represented by A include cycloalkenyl having 3 to 8 carbon atoms, preferably 5 to 7 cycloalkenyl, for example, cyclopentenyl, cyclohexenyl. The optionally substituted phenyl represented by A include unsubstituted phenyl and substituted phenyl. The optionally substituted heterocyclic group represented by A include unsubstituted heterocyclic groups and substituted heterocyclic groups. The unsubstituted heterocyclic groups are, for example, 5 to 6 membered heterocyclic groups containing in the ring 1 to 3 heteroatoms selected from oxygen, sulfur and nitrogen, which may form condensed ring systems with carbocyclic rings or other heterocyclic rings. Examples of the unsubstituted heterocyclic group include pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, thiazolyl, benzothiazolyl, benzofuranyl, benzothienyl, oxazolyl, benzoxazolyl, isoxazolyl, pyrazolyl, imidazolyl, quinolyl. Examples of the substituent of the substituted phenyl or substituted heterocyclic groups represented by A include lower alkyl (e.g., methyl, ethyl, propyl, butyl, etc.), lower alkenyl (e.g., vinyl, allyl, crotyl, etc.), lower alkynyl (e.g., ethynyl, propargyl, butynyl), cycloalkyl (e.g., cyclopropyl, cyclopentyl, cyclohexyl, cycloalkenyl (e.g., cyclopentenyl, cyclohexenyl, lower alkanoyl (e.g., acetyl, propionyl, isobutyryl, lower alkylsilyl (e.g., methylsilyl, ethylsilyl, propylsilyl, butylsilyl), halogenated lower alkyl (e.g., trifluoromethyl, chloromethyl, 2-bromoethyl, 1,2-dichloropropyl), di(lower)alkylamino (e.g., dimethylamino, diethylamino), phenyl, phenyl(lower)alkyl (e.g., benzyl, phenethyl), phenyl(lower)alkenyl (e.g., styryl, cinnamyl), furyl(lower)alkyl (e.g., 3-furylmethyl, 2-furylethyl), furyl(lower)alkenyl (e.g., 3-furylvinyl, 2-furylallyl), halogen (e.g., fluorine, chlorine, bromine, iodine), nitro, cyano, -OR 4 [wherein R 4 is hydrogen, lower alkyl (e.g., methyl, ethyl, propyl), lower alkenyl (e.g., vinyl, allyl, crotyl), lower alkynyl (e.g., ethynyl, 2-propynyl, 3-butynyl), lower alkanoyl (e.g., acetyl, propionyl, butyryl), phenyl, lower alkoxyphenyl (e.g., 3-methoxyphenyl, 4-ethoxyphenyl), nitrophenyl (e.g., 3-nitrophenyl, 4-nitrophenyl), phenyl(lower)alkyl (e.g., benzyl, phenethyl, phenylpropyl), cyanophenyl(lower)alkyl (e.g., 3-cyanophenylmethyl, 4-cyanophenylethyl), benzoyl, tetrahydropyranyl, pyridyl, trifluoromethylpyridyl, pyrimidinyl, benzothiazolyl, quinolyl, benzoyl(lower)alkyl (e.g., benzoylmethyl, benzoylethyl), benzenesulfonyl or lower alkylbenzenesulfonyl (e.g., toluenesulfonyl)] and -CH 2 -Z-R 5 [wherein Z is -O-, -S- or -NR 6 - (wherein R 6 is hydrogen or lower alkyl), R 5 is phenyl, halophenyl (e.g., 2-chlorophenyl, 4-fluorophenyl), lower alkoxyphenyl (e.g., 2-methoxyphenyl, 4-ethoxyphenyl), pyridyl or pyrimidinyl]. These substituents of the phenyl or heterocyclic group represented by A may be at any possible position on the ring and may be the same or different. The number of the substituents is 1 to 5, preferably 1 to 4, more preferably 1 to 3. Examples of the halogen represented by X include fluorine, chlorine, bromine and iodine. In the processes of the present invention, A is preferably optionally substituted phenyl such as unsubstituted phenyl or phenyl substituted with lower alkyl and/or halogen; or an optionally substituted heterocyclic group such as unsubstituted pyridyl or pyridyl substituted with halogen and/or halogenated lower alkyl. B is preferably -O-, -CH 2 O- or -OCH 2 -. In the processes of the present invention, A is more preferably phenyl substituted with mono- or dimethyl and/or chlorine or fluorine (e.g., 2-methylphenyl, 2,5-dimethylphenyl, 3,5-dimethylphenyl, 3,4-dimethylphenyl, 4-fluorophenyl, 4-chlorophenyl, 2-methyl-4-chlorophenyl,) or pyridyl optionally substituted with chlorine and/or trifluoromethyl (e.g., pyridyl, 2-chloropyridyl, 3,5-dichloropyridyl, 2-trifluoromethylpyridyl, 3-trifluoromethylpyridyl, 5-trifluoromethylpyridyl, 2-chloro-3-trifluoromethylpyridyl, 2-chloro-5-trifluoromethylpyridyl, 5-chloro-3-trifluoromethylpyridyl, 3-chloro-5-trifluoromethylpyridyl, 6-chloro-3-trifluoromethylpyridyl). B is more preferably -O- or -OCH 2 . R is preferably methyl. R 1 is preferably hydrogen. R 2 is preferably methyl. The compound (II), (III) and (IV) may be any of its E-isomer, Z-isomer or mixtures of the E- and Z-isomers. This is indicated by the wave line (∼) in the formulas. The compound (I) is an E-isomer. Specific examples of the desired alkoxyiminoacetamide compound (I) are described below (see U.S. Patent No. 5185342 and JP-A 4-182461). N-methyl-2-[2-(2,5-dimethylphenoxymethyl)phenyl]-2-methoxyiminoacetamide; 2-(2-phenoxyphenyl)-2-methoxyiminoacetamide; N,N-dimethyl-2-(2-phenoxyphenyl)-2-methoxyiminoacetamide; N-methyl-2-(2-phenoxyphenyl)-2-methoxyiminoacetamide; N-methyl-2-[2-(3-tolyloxy)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(4-nitrophenoxy)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(2-nitrophenoxy)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(4-acetylphenoxy)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(4-chlorophenoxy)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(4-bromophenoxy)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(4-t-butylphenoxy)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(4-methoxyphenoxy)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(4-trimethylsilylphenoxy)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(4-iodophenoxy)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(4-chloro-3-methylphenoxy)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(2-tolyloxy)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(4-tolyloxy)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(2,4-diisopropylphenoxy)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(4-isopropylphenoxy)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(3,4-dichlorophenoxy)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(3-benzyloxyphenoxy)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(3-methoxyphenoxy)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(3-phenoxyphenoxy)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(4-phenoxyphenoxy)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(2,4-dichloro-5-phenoxyphenoxy)-phenyl]-2-methoxyiminoacetamide; N-methyl-2-(2-benzyloxyphenyl)-2-methoxyiminoacetamide; N-methyl-2-(2-phenoxymethylphenyl)-2-methoxyiminoacetamide; N-methyl-2-[2-(3-phenoxyphenoxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(4-bromophenoxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(3-methoxyphenoxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(3-chlorophenoxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(2-chlorophenoxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(4-styrylphenoxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(4-benzoylphenoxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(4-t-butylphenoxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(4-methylphenoxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(4-cyanophenoxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(2,4-dichlorophenoxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(3,4-dichlorophenoxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(3,5-dichlorophenoxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(3-trifluoromethylphenoxymethyl)-phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(3-dimethylaminophenoxymethyl)-phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(3-bromophenoxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(3-nitrophenoxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(4-fluorophenoxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(3-isopropoxyphenoxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(4-chlorophenoxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-(2-phenylthiomethylphenyl)-2-methoxyiminoacetamide; N-methyl-2-(2-phenylsulfinylmethylphenyl)-2-methoxyiminoacetamide; N-methyl-2-[2-(3-methyl-2-butenyloxy)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(3,7-dimethyl-2,6-octadienyloxy)-phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(3,3-dichloro-2-propenyloxy)-phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(5-trifluoromethylpyridin-2-yloxy)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(3-trifluoromethylpyridin-2-yloxy)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(5-trifluoromethylpyridin-2-yloxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(2-pyrimidinyloxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(2-pyridyloxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-(2-phenylthiophenyl)-2-methoxyiminoacetamide; N-methyl-2-[2-(3-hydroxyphenoxy)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(3-tetrahydropyran-2-yloxyphenoxy)-phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(3-pyrimidin-2-yloxyphenoxy)-phenyl]-2-methoxyiminoacetamide; N-methyl-2-{2-[3-(5-trifluoromethylpyridin-2-yloxy)phenoxy]phenyl}-2-methoxyiminoacetamide; N-methyl-2-{2-[3-(3-methoxyphenoxy)phenoxy]-phenyl}-2-methoxyiminoacetamide; N-methyl-2-{2-[3-(2-nitrophenoxy)phenoxy]phenyl}-2-methoxyiminoacetamide; N-methyl-2-[2-(3-quinolin-2-yloxyphenoxy)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(3-benzothiazol-2-yloxyphenoxy)-phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(3-benzoylmethyloxyphenoxy)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(3-toluenesulfonyloxyphenoxy)-phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(3-acetyloxyphenoxy)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(3-benzoyloxyphenoxy)phenyl]-2-methoxyiminoacetamide; N-methyl-2-{2-[3-(2-cyanobenzyloxy)phenoxy]-phenyl}-2-methoxyiminoacetamide; N-methyl-2-{2-[3-(2-propynyloxy)phenoxy]phenyl}-2-methoxyiminoacetamide; N-methyl-2-[2-(3-styryloxyphenoxy)phenyl]-2-methoxyiminoacetamide; N-methyl-2-{2-[3-(2-furan-2-ylvinyl)phenoxy]-phenyl}-2-methoxyiminoacetamide; N-methyl-2-[2-(4-hydroxyphenoxy)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(4-benzyloxyphenoxy)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(3-benzyloxyphenoxy)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(3-phenylthiomethylphenoxy)phenyl]-2-methoxyiminoacetamide; N-methyl-2-{2-[3-(N-methylanilinomethyl)phenoxy]-phenyl}-2-methoxyiminoacetamide; N-methyl-2-{2-[3-(2-pyridyloxymethyl)phenoxy]-phenyl}-2-methoxyiminoacetamide; N-methyl-2-{2-[3-(phenylsulfinylmethyl)phenoxy]-phenyl}-2-methoxyiminoacetamide; N-methyl-2-{2-[3-(pyrimidin-2-yloxymethyl)-phenoxy]phenyl}-2-methoxyiminoacetamide; N-methyl-2-{2-[3-(4-methoxyphenoxymethyl)-phenoxy]phenyl)-2-methoxyiminoacetamide; N-methyl-2-{2-[3-(4-bromophenoxymethyl)phenoxy]-phenyl}-2-methoxyiminoacetamide; N-methyl-2-[2-(3-phenoxymethylphenoxy)phenyl]-2-methoxyiminoacetamide; N-methyl-2-(2-(E)-styrylphenyl)-2-methoxyiminoacetamide; N-methyl-2-(2-(Z)-styrylphenyl)-2-methoxyiminoacetamide; N-methyl-2-{2'-[(1"S*, 2"R*)-1",2"-epoxy-2"-phenylethyl]phenyl}-2-methoxyiminoacetamide; N-methyl-2-{2'-[(1"R*,2"R*)-1",2"-epoxy-2"-phenylethyl]phenyl}-2-methoxyiminoacetamide; N-methyl-2-(2-phenylethylphenyl)-2-methoxyiminoacetamide; N-methyl-2-[2-(α-hydroxybenzyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-(2-benzoylphenyl)-2-methoxyiminoacetamide; N-methyl-2-[2-(2-phenylphenoxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(3-phenylphenoxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(4-phenylphenoxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(2-isopropoxyphenoxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(4-isopropoxyphenoxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-{2-[2-(2-propynyloxy)phenoxymethyl]-phenyl}-2-methoxyiminoacetamide; N-methyl-2-(2-[3-(2-propynyloxy)phenoxymethyl]-phenyl}-2-methoxyiminoacetamide; N-methyl-2-{2-[4-(2-propynyloxy)phenoxymethyl]-phenyl}-2-methoxyiminoacetamide; N,N-dimethyl-2-[2-(4-trifluoromethylthiophenoxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(2-fluorophenoxymethyl)phenyl]-2-methoxyiminoacetamide; N,N-dimethyl-2-[2-(3-fluorophenoxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(2-trifluoromethylphenoxymethyl)-phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(4-trifluoromethylphenoxymethyl)-phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(2,3-dimethylphenoxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(2,4-dimethylphenoxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(2,5-dimethylphenoxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(2,6-dimethylphenoxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(3,4-dimethylphenoxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(3,5-dimethylphenoxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(indan-5-yloxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(2,3-difluorophenoxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(2,5-difluorophenoxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(2,6-difluorophenoxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(3,4-difluorophenoxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(3,5-difluorophenoxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(2,3-dichlorophenoxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(2,5-dichlorophenoxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(2,6-dichlorophenoxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(4-chloro-2-methylphenoxymethyl)-phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(4-chloro-3-methylphenoxymethyl)-phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(4-chloro-3-ethylphenoxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(3-chloro-5-methoxyphenoxymethyl)-phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(2,3,5-trimethylphenoxymethyl)-phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(2,3,6-trimethylphenoxymethyl)-phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(2,4,6-trimethylphenoxymethyl)-phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(2,4,5-trichlorophenoxymethyl)-phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(2,4,6-trichlorophenoxymethyl)-phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(2,3,5-trichlorophenoxymethyl)-phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(2,3,6-trichlorophenoxymethyl)-phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(4-chloro-3,5-dimethylphenoxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(2-chloro-4,5-dimethylphenoxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(2,3,5,6-tetrafluorophenoxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(2,3,4,5,6-pentafluorophenoxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(3-chloro-5-trifluoromethylpyridin-2-yloxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(3,5-dichloropyridin-2-yloxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(6-chloropyridin-2-yloxymethyl)-phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(6-chloro-3-trifluoromethylpyridin-2-yloxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(6-chloro-5-trifluoromethylpyridin-2-yloxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(2-benzothiazolyloxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(2-benzoxazolyloxymethyl )phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(7-coumarinyloxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(1-naphthyloxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(2-naphthyloxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(4-chloro-1-naphthyloxymethyl)-phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(6-bromo-2-naphthyloxymethyl)-phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(2-methyl-l-naphthyloxymethyl)-phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(1-bromo-2-naphthyloxymethyl)-phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(3-allyloxyphenoxy)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(3-cyanomethoxyphenoxy)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(3-trifluoromethylphenoxy)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(4-fluorophenoxy)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(2,5-dimethylphenoxy )phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(4-chloro-3-methylphenoxy)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(3,4-dimethylphenoxy)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(3,5-dimethylphenoxy)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(2,3-dimethylphenoxy)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(2,4-dimethylphenoxy)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(2,3,4-trimethylphenoxy)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(3,4,5-trimethylphenoxy)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(4-fluorophenoxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(2,4-difluorophenoxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(2-methylphenoxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(3-methylphenoxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(6-methoxypyridin-2-yloxymethyl)-phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(3,6-dichloro-5-trifluoromethylpyridin-2-yloxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(5-trifluoromethylpyridin-2-yloxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(3-trifluoromethylpyridin-2-yloxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(6-trifluoromethylpyridin-2-yloxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(5-chloro-3-trifluoromethyl-pyridin-2-yloxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(6-methylthiopyridin-2-yloxy-methyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(6-isopropoxypyridin-2-yloxy-methyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(6-methoxy-3-trifluoromethyl-pyridin-2-yloxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(6-methylthio-3-trifluoromethylpyridin-2-yloxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(6-isopropoxy-3-trifluoromethylpyridin-2-yloxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(6-methoxy-5-trifluoromethylpyridin-2-yloxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(6-isopropoxy-5-trifluoromethylpyridin-2-yloxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(6-methylthio-5-trifluoromethylpyridin-2-yloxymethyl)phenyl]-2-methoxyiminoacetamide; N-methyl-2-[2-(2-chloropyridin-3-yloxymethyl)-phenyl]-2-methoxyiminoacetamide. In a preferred process embodying the present invention, the compound (I) can be prepared according to the following steps. Step 1: Conversion of the compound (II) into the compound (III): The compound (II) is treated with a base in a solvent to give a salt of the compound (III). Examples of the base include alkaline or alkaline earth metal hydroxides (e,g, sodium hydroxide, potassium hydroxide), alkaline or alkaline earth metal carbonates (e.g., sodium carbonate, potassium carbonate ), alkaline or alkaline earth metal alkoxides (e.g., sodium methoxide, sodium ethoxide, potassium t-butoxide). The amount of the base to be used is normally 1 to 20 mol, preferably 1 to 3 mol per mol of the compound (II). Examples of the solvent include N,N-dimethylformamide, dimethyl sulfoxide, hydrocarbons (e.g., toluene, benzene, xylene, cyclohexane, hexane), alcohols (e.g., methanol, ethanol, isopropanol, butanol), ethers (e.g., tetrahydrofuran, dioxane), water. These solvents can be used alone or as mixtures thereof. The reaction temperature is normally 20 to 200°C, preferably 50 to 180°C. The reaction time is normally 0.05 to 100 hours, preferably 1 to 48 hours. The salt of the compound (III) thus obtained can be used in the next step as the reaction mixture or the crude product, or after purification by conventional methods. If necessary, the compound (III) may be isolated from its salt, for example, by treatment of the salt with an appropriate acid optionally after removal of impurities by washing the-salt with an appropriate organic solvent. Examples of the acid include hydrohalogenic acids (e.g., hydrochloric acid, hydrobromic acid), sulfuric acid, sulfonic acids (e.g., trifluoromethanesulfonic acid, toluenesulfonic acid). Step 2: Conversion of the compound (III) into the compound (IV): The compound (III) is reacted with a halogenating agent in the absence of a solvent or in an appropriate solvent in the presence or absence of a catalyst to give the compound (IV). Examples of the halogenating agent include thionyl chloride, phosphoryl chloride, phosphorus pentachloride, phosphorus trichloride, phosgene, thionyl bromide, phosphoryl bromide, phosphorus pentabromide, phosphorus tribromide, oxalyl chloride. The amount of the halogenating agent to be used is normally 1 to 10 mol, preferably 1 to 3 mol per mol of the compound (III). The catalyst is not necessarily used. When it is used, it can appropriately be selected from N,N-dimethylformamide, dimethyl sulfoxide, hexamethylphosphoric triamide, pyridine, triethylamine, iodine, zinc chloride, Vilsmeyer reagent. The amount of the catalyst to be used is normally 0.005 to 10 mol, preferably 0.01 to 1 mol per mol of the compound (III). The solvent is not necessarily used. When it is used, hydrocarbons (e.g., toluene, benzene, xylene, hexane, cyclohexane), halogenated hydrocarbons (e.g., methylene chloride, dichloroethane) can be used alone or as mixtures thereof. The reaction temperature is generally -50 to 160°C, preferably 0 to 120°C. The reaction time is 5 to 24 hours. The compound (IV) thus obtained can be used in the next step as the reaction mixture or the crude product, or after purification by conventional methods. Step 3: Conversion of the compound (IV) to the compound (I): The compound (IV) is reacted with an amine in the absence of a solvent or in an appropriate solvent in the presence or absence of a base to give the compound (I). The amine is a compound of the formula: HNR 1 R 2 (wherein R 1 and R 2 are as defined above) and may be primary amines, secondary amines or ammonia. Examples of the primary amines or secondary amines include lower alkylamines or di(lower)alkylamines each having lower alkyl described above for R 1 and R 2 . The amount of the amine to be used is normally 1 to 20 mol, preferably 1 to 5 mol per mol of the compound (IV). The base may be used to trap the resulting acid. Alternatively, an excess amount of the above amine as the reagent can be used in place of the base. When the base is used, it can be selected from pyridine, triethylamine, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium methoxide, sodium ethoxide, potassium t-butoxide. The amount of the base to be used is normally 1 to 20 mol, preferably 1 to 3 mol per mol of the compound (IV). When a solvent is used, it can appropriately be selected from hydrocarbons (e.g., toluene, benzene, xylene, cyclohexane, hexane), halogenated hydrocarbons (e.g., methylene chloride, dichloroethane), ethers (e.g., tetrahydrofuran, dioxane), water. These solvents can be used alone or as mixtures thereof. When the amine or base described above is liquid, it can also be used as the solvent. The reaction temperature is normally -50 to 160°C, preferably 0 to 120°C. The reaction time is normally 0.1 to 24 hours, preferably 0.5 to 12 hours. The alkoxyiminoacetamide compound (I) thus obtained is generally a mixture of the E- and Z-isomers. The mixture as it is can be used for agricultural fungicides. Since the E-isomer generally has superior fungicidal activity to that of the Z-isomer, the E-isomer content is preferably increased. In general, isomerization of Z-isomers to E-isomers proceeds under acidic conditions. Such isomerization may sometimes occur more or less in any of the above steps under acidic conditions. However the compound (I) obtained in the last step is treated with an acid for isomerization to increase the E-isomer content. If necessary, the compound (I) may be separated and purified from the reaction mixture before the isomerization. The isomerization with an acid can be carried out by treating the compound (I) with an acid in an appropriate solvent. Examples of the acid include hydrohalogenic acids (e.g., hydrochloric acid, hydrobromic acid), hydrogen halides (e.g., hydrogen chloride, hydrogen bromide), sulfonic acids (e.g., toluenesulfonic acid), thionyl chloride, oxalyl chloride, aluminium chloride, aluminium bromide, titanium trichloride, titanium tetrachloride. These acids can be used alone or as mixtures thereof. The amount of the acid is normally 0.001 to 20 mol, preferably 0.01 to 2 mol per mol of the compound (I). Examples of the solvent include hydrocarbons (e.g., benzene, toluene, xylene), halogenated hydrocarbons (e.g., methylene chloride, 1,2-dichloroethane), ethers (e.g., tetrahydrofuran, dioxane), ketones (e.g., acetone, ethyl methyl ketone). Among them, hydrocarbons (e.g., benzene) and halogenated hydrocarbons (e.g., methylene chloride, 1,2-dichloroethane ) are preferred. The reaction temperature is normally 0 to 150°C, preferably 20 to 110°C. The compound (II) used as the starting material in the above step 1 can be prepared according to the method described in Japanese Patent Application No. 5-273556. For example, the compound (II) wherein B is -OCH 2 - can be obtained according to the process of the following scheme. wherein each symbol is as defined above. Firstly, the compound (V) is reacted with excess α,α'-o-dihalogenoxylene (VI) in an appropriate solvent in the presence of a base in the presence or absence of a phase-transfer catalyst. Examples of the α,α'-o-dihalogenoxylene (VI) to be used include α,α'-o-dichloroxylene, α,α'-o-dibromoxylene, α,α'-o-diiodoxylene. The amount of the α,α'-o-dihalogenoxylene (VI) to be used is 1 to 10 mol, preferably 3 to 5 mol per mol of the compound (V). When the reaction is carried out without using excess α,α'-o-dihalogenoxylene (VI), the compound (X) of the formula: wherein each symbol is as defined above, is produced in a large amount. Examples of the solvent to be used include the same solvents as those described for the above reaction using the alkaline metal cyanide. These solvents can be used alone or in combination thereof. Examples of the base to be used include sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium methoxide, sodium ethoxide, potassium tert-butoxide. The amount of the base to be used is 1 to 5 mol, preferably 1 to 2 mol per mol of the compound (V). Examples of the phase-transfer catalyst include the same phase-transfer catalysts as those described for the above reaction using the alkaline metal cyanide. The amount of the phase-transfer catalyst to be used is 0.01 to 0.2 mol, preferably 0.05 to 0.1 mol per mol of the compound (V). The reaction temperature is normally 0 to 120°C, preferably 20 to 100°C. The reaction time is generally 20 minutes to 12 hours, preferably 30 minutes to 3 hours. The remaining α,α'-o-dihalogenoxylene (VI) is removed from the crude benzyl halide (VII) thus obtained. The resulting residue can be used in the next step as it is or after purification by conventional methods. Then, the benzyl halide (VII) is reacted with an alkaline metal cyanide in an appropriate solvent in the presence or absence of a phase-transfer catalyst to obtain the benzyl cyanide (VIII). Examples of the alkaline metal cyanide to be used include sodium cyanide, potassium cyanide. The amount of the alkaline metal cyanide to be used is 1 to 5 mol, preferably 1 to 2 mol per mol of the benzyl halide (VII). Examples of the solvent to be used include acetone, acetonitrile, methyl ethyl ketone, dimethylformamide (DMF), dimethyl sulfoxide (DMSO), toluene, methanol, ethanol, isopropanol, butanol, tetrahydrofuran (THF), dioxane, water. These solvents can be used alone or in combination thereof. Examples of the phase-transfer catalyst include tetra-n-butylammonium chloride, tetra-n-butylammonium bromide, tetra-n-butylammmonium hydrogensulfate, tetra-methylammmonium bromide, benzyltriethylammonium chloride, tris(3,6-dioxaheptyl)amine. The amount of the phase-transfer catalyst to be used is 0.01 to 0.2 mol, preferably 0.05 to 0.1 mol per mol of the benzyl halide (VII). The reaction temperature is normally 10 to 120°C, preferably 20 to 100°C. The reaction time is generally 10 minutes to 24 hours, preferably 30 minutes to 5 hours. The benzyl cyanide (VIII) thus obtained can be used in the next step as the reaction mixture or the crude product, or after purification by conventional methods. Then, the above benzyl cyanide (VIII) is reacted with an alkyl nitrite for formation of an oxime in an appropriate solvent in the presence of a base in the presence or absence of a phase-transfer catalyst to obtain α-hydroxyiminobenzyl cyanide (IX). Examples of the alkyl nitrite to be used include methyl nitrite, ethyl nitrite, propyl nitrite, isopropyl nitrite, butyl nitrite, isoamyl nitrite. The amount of the alkyl nitrite to be used is 1 to 5 mol, preferably 1 to 2 mol per mol of the benzyl cyanide (VIII). Examples of the solvent to be used include the same solvents as those described for the above reaction using the alkaline metal cyanide. These solvent can be used alone or in combination thereof. Examples of the base to be used include sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium methoxide, sodium ethoxide, potassium tert-butoxide. The amount of the base to be used is 1 to 5 mol, preferably 1 to 2 mol per mol of the benzyl cyanide (VIII). Examples of the phase-transfer catalyst include the same phase-transfer catalysts as those described for the above reaction using the alkaline metal cyanide. The amount of the phase-transfer catalyst to be used is 0.01 to 0.2 mol, preferably 0.05 to 0.1 mol per mol of the benzyl cyanide (VIII). The reaction temperature is normally 0 to 120°C, preferably 20 to 50°C. The reaction time is generally 5 minutes to 12 hours, preferably 30 minutes to 3 hours. The α-hydroxyiminobenzyl cyanide (IX) thus obtained can be used in the next step as the reaction mixture or the crude product, or after purification by conventional methods. Then, the above α-hydroxyiminobenzyl cyanide (IX) is reacted with an alkylating agent in an appropriate solvent in the presence of a base in the presence or absence of a phase-transfer catalyst to obtain α-alkoxyiminobenzyl cyanide (II'). Examples of the alkylating agent to be used include dialkyl sulfates (e.g., dimethyl sulfate), alkyl halides (e.g., methyl chloride, methyl bromide, methyl iodide). The amount of the alkylating agent to be used is 1 to 5 mol, preferably 1 to 2 mol per mol of the α-hydroxyiminobenzyl cyanide (IX). Examples of the base to be used include sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium methoxide, sodium ethoxide, potassium tert-butoxide. The amount of the base to be used is 1 to 5 mol, preferably 1 to 2 mol per mol of the α-hydroxyiminobenzyl cyanide (IX). Examples of the solvent to be used include the same solvents as those described for the above reaction using the alkaline metal cyanide. These solvents can be used alone or in combination thereof. Examples of the phase-transfer catalyst include the same phase-transfer catalysts as those described for the above reaction using the alkaline metal cyanide. The amount of the phase-transfer catalyst to be used is 0.01 to 0.2 mol, preferably 0.05 to 0.1 mol per mol of the α-hydroxyiminobenzyl cyanide (IX). The reaction temperature is normally 0 to 120°C, preferably 0 to 30°C. The reaction time is generally 5 minutes to 12 hours, preferably 15 minutes to 2 hours. Alternatively, the benzyl cyanide (VIII) is reacted with an alkyl nitrite under the same conditions as those described for the conversion of the compound (VIII) to the compound (IX). Then, an alkylating agent is added to the reaction mixture for the alkylation. Thus, α-alkoxyiminobenzyl cyanide (II') can be obtained by one-pot synthesis. The α-alkoxyiminobenzyl cyanide thus obtained can be used in the next step as the reaction mixture or the crude product, or after purification by conventional methods. The alkoxyiminoacetamide (I) obtained by the process of the present invention can be used as agricultural fungicides, for example, according to the method described in U.S. Patent No. 5185342 the disclosure of which is incorporated herein by reference. As described hereinabove, according to the present invention, there is provided a process for producing alkoxyiminoacetamide compound (I). This process gives the compound in high yield. Further, since the content of the desired compound, particularly its E-isomer, in the end product is high, the compound can easily be purified and has excellent fungicidal activity. The following examples further illustrate the present invention in detail. Example 1 Synthesis of 2-(2,5-dimethylphenoxymethyl)benzyl chloride Potassium carbonate (55.28 g, 0.4 mol), α,α'-o-dichloroxylene (175.06 g, 1.0 mol) and acetone (200 ml) were added to 2,5-xylenol (24.43 g, 0.2 mol). The mixture was heated under reflux for 8 hours. After completion of the reaction, the resulting insoluble materials were removed, and excess α,α'-o-dichloroxylene was evaporated under reduced pressure to obtain 2-(2,5-dimethylphenoxymethyl)benzyl chloride (53.20 g, Yield: 88.5%, Purity: 86.8%) as a colorless oil. Example 2 Synthesis of 2-(2,5-dimethylphenoxymethyl)benzyl chloride 95% sodium hydroxide (13.89 g, 0.33 mol) and water (60 ml) were added to 2,5-xylenol (36.65 g, 0.3 mol) and dissolved while heating. Then water was evaporated under reduced pressure. α,α'-o-Dichloroxylene (105.04 g, 0.6 mol) and acetone (150 ml) were added to the resulting sodium salt, and the mixture was heated under reflux for 1 hour. After completion of the reaction, the resulting insoluble materials were removed. After distillation under reduced pressure, 2-(2,5-dimethylphenoxymethyl)benzyl chloride (39.07 g, Yield: 49.9%) was obtained as colorless crystals. bp 145-147°C/0.6 mmHg, mp 46.5-48.5°C. 1 H-NMR (CDCl 3 ) δ ppm: 2.21(s,3H), 2.34(s,3H), 4.74(s,2H), 5.18(s,2H), 6.71-7.54(m,7H). Example 3 Synthesis of (Z)-2-[2-(2,5-dimethylphenoxymethyl)phenyl]-2-methoxyiminoacetic acid To (Z)-2-(2,5-dimethylphenoxymethyl)-α-methoxyiminobenzyl cyanide (0.59 g, 2 mmol) were added 85% potassium hydroxide (0.26 g, 4 mmol), butanol (4 ml) and water (0.4 ml). The mixture was stirred under reflux for 7 hours. After completion of the reaction, water (100 ml) was added. The resulting mixture was adjusted to pH of not more than 3 by adding 6N aqueous hydrochloric acid solution, extracted with methylene chloride (50 ml) twice, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give crystals (0.60 g), which were then recrystallized from n-hexane to give (Z)-2-[2-(2,5-dimethylphenoxymethyl)phenyl]-2-methoxyiminoacetic acid (0.42 g, Yield: 67.0%). mp: 112.5-113.5°C 1 H-NMR (CDCl 3 ) δ ppm: 2.21(3H,s), 2.29(3H,s), 2.65(1H,brs), 4.09(3H,s), 5.20(2H,s), 6.64-7.63(7H,m). Example 4 Synthesis of 2-[2-(2,5-dimethylphenoxymethyl)-phenyl]-2-methoxyiminoacetic acid To 2-(2,5-dimethylphenoxymethyl)-α-methoxyiminobenzyl cyanide (E/Z=13/87)(2.94 g, 10 mmol) were added 96.7% potassium hydroxide (1.16 g, 20 mmol), butanol (20 ml) and water (2 ml). The mixture was stirred under reflux for 13 hours. After completion of the reaction, 1N aqueous hydrochloric acid solution (150 ml) was added. The mixture was extracted with toluene (150 ml), washed with water (100 ml), dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give crude 2-[2-(2,5-dimethylphenoxymethyl)phenyl]-2-methoxyiminoacetic acid (2.99 g, Yield 95.5%, Z= at least 99%). Example 5 Synthesis of 2-[2-(2,5-dimethylphenoxymethyl)phenyl]-2-methoxyimino-N-methylacetamide Toluene (10 ml), thionyl chloride (1.36 g, 11 mmol) and dimethylformamide (DMF) (0.1 ml) were added to the crude 2-[2-(2,5-dimethylphenoxymethyl)phenyl]-2-methoxyiminoacetic acid (Z= at least 99%)(2.99 g, 9.5 mmol), and the mixture was stirred at 70°C for 1.5 hours. After completion of the reaction, the mixture was concentrated to give crude 2-[2-(2,5-dimethylphenoxymethyl)phenyl]-2-methoxyiminoacetyl chloride (E/Z=75/25). 1 H-NMR (CDCl 3 ) δ ppm: 2,18(2.25H,s), 2.27(0.75H,s), 2.29(2.25H,s), 2.32(0.75H,s), 4.04(0.75H,s), 4.12(2.25H,s), 4.88(1.5H,s), 5.26(0.5H,s), 6.67-7.57(7H,m). The resulting crude product was dissolved in dry toluene (10 ml), the solution was added dropwise to a suspension of 40% aqueous methylamine solution (2.96 g, 38 mmol) and toluene (10 ml) under ice-cooling over 20 minutes, and the mixture was stirred at room temperature for 2 hours. After completion of the reaction, water (100 ml) was added. The resulting mixture was adjusted to pH of not more than 3 by adding 6N aqueous hydrochloric acid solution, extracted with ether (150 ml), dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give 2-[2-(2,5-dimethylphenoxymethyl)phenyl]-2-methoxyimino-N-methylacetamide (2.64 g, Yield: 84.8%, E/Z=75/25). Example 6 Synthesis of (E)-2-[2-(2,5-dimethylphenoxymethyl)-phenyl]-2-methoxyimino-N-methylacetamide Toluene (3 ml) and conc. hydrochloric acid (0.61 g, 6 mmol) were added to 2-[2-(2,5-dimethylphenoxymethyl)phenyl]-2-methoxyimino-N-methylacetamide (0.98 g, E/Z=75/25), and the mixture was stirred at 80°C for 2 hours. After completion of the reaction, water (150 ml) was added. The mixture was extracted with methylene chloride (50 ml) twice, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give crystals (1.01 g, E/Z=95/5). The crystals were recrystallized from toluene to give (E)-2-[2-(2,5-dimethylphenoxymethyl)-phenyl]-2-methoxyimino-N-methylacetamide (0.72 g, Yield 71.5%) as colorless crystals. mp: 136-137°C. 1 H-NMR (CDCl 3 ) δ ppm: 2.18(3H,s), 2.29(3H,s), 2.88(3H,d,J=4.9Hz), 3.95(3H,s), 4.92(2H,s), 6.62-7.57(8H,m). Examples 7 to 10 Synthesis of 2-[2-(2,5-dimethylphenoxymethyl)-phenyl]-2-methoxyiminoacetic acid To 2-(2,5-dimethylphenoxymethyl)-α-methoxyiminobenzyl cyanide (E/Z=13/87)(2.94 g, 10 mmol) were added 96.7% potassium hydroxide (1.16 g, 20 mmol) and a solvent shown in Table 1. The mixture was subjected to reaction under conditions shown in Table 1. After completion of the reaction, 1N aqueous hydrochloric acid solution (150 ml) was added. The mixture was extracted with toluene (150 ml), washed with water (100 ml), dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give crude 2-[2-(2,5-dimethylphenoxymethyl)phenyl]-2-methoxyiminoacetic acid. The crude product was subjected to HPLC analysis to calculate the yield. Example Solvent (liter/mol) Reaction conditions Yield (%) E/Z ratio 7 PhMe (2.0)/ MeOH (0.2) reflux, 13 h 52 59/41 8 PhMe (2.0)/ H 2 O (0.2)/ MeOH (0.2) reflux, 20 h 76 26/74 9 MeOH (1.0)/ H 2 O (0.5) reflux, 22 h (internal tem-) perature: 74°C) 90 10/90 10 PhMe (0.3)/ H 2 O (O.5)/ MeOH (0.7) reflux, 21 h (internal temperature-: 74°C) 93 24/76 Example 11 Synthesis of 2-[2-(2,5-dimethylphenoxymethyl)-phenyl]-2-methoxyimino-N-methylacetamide 2-[2-(2,5-Dimethylphenoxymethyl)phenyl]-2-methoxyiminoacetic acid (9.40 g, 30 mmol, E/Z=20/80) was dissolved in dimethylformamide (DMF)(0.11 g, 1.5 mmol) and toluene (20 ml). A solution of 95% thionyl chloride (4.13 g, 33 mmol) and toluene (10 ml) was added dropwise at 60°C over 5 hours. The mixture was stirred at 60°C for 5 hours. After completion of the reaction, the mixture was concentrated under reduced pressure to a total amount of 30 g to give crude 2-[2-(2,5-dimethylphenoxymethyl)phenyl]-2-methoxyiminoacetyl chloride. A half amount of the crude product thus obtained was added dropwise to a suspension of 40% aqueous methylamine solution (2.8 g, 36.1 mmol), water (10 g) and toluene (10 g) at 20 to 25°C over 1 hour. The other half of the crude product and 28.8% aqueous potassium hydroxide solution (4.2 g, 30 mmol) were added separately and simultaneously at 20 to 25°C over 1 hour. The mixture was stirred at 20 to 25°C for 1.5 hours. After completion of the reaction, the mixture was acidified by adding 1N aqueous hydrochloric acid solution (10 ml) and extracted with ethyl acetate (100 ml). The ethyl acetate layer was washed with saturated brine (150 ml) twice, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give crystals of 2-[2-(2,5-dimethylphenoxymethyl)phenyl]-2-methoxyimino-N-methylacetamide (Purity: 95.4 %, determined by HPLC analysis)(9.81 g, Yield in terms of the pure product: 95.6%, E/Z=93/7). Example 12 Isomerization of 2-[2-(2,5-dimethylphenoxymethyl)-phenyl]-2-methoxyiminoacetamide (1) Toluene (5 ml) and thionyl chloride (0.12 g, 1 mmol) were added to 2-[2-(2,5-dimethylphenoxymethyl)phenyl]-2-methoxyiminoacetamide (1.56 g, 5 mmol, E/Z=9/91). The mixture was stirred at 80°C for 8 hours. After completion of the reaction, water (50 ml) was added. The resulting mixture was extracted with toluene (50 ml) twice, washed with 1N aqueous sodium hydroxide solution, water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give colorless crystals (1.53 g)(Yield: 98%, E/Z=97/3). (2) Toluene (5 ml) and titanium trichloride (25% diluted hydrochloric acid solution) (0.15 g, 0.25 mmol) were added to 2-[2-(2,5-dimethylphenoxymethyl)phenyl]-2-methoxyiminoacetamide (1.56 g, 5 mmol, E/Z=9/91). The mixture was stirred at 80°C for 8 hours. After completion of the reaction, water (50 ml) was added. The resulting mixture was extracted with toluene (50 ml) twice, washed with 1N aqueous sodium hydroxide solution, water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give pale orange crystals (1.51 g)(Yield: 97%, E/Z=96/4). (3) Toluene (5 ml) and titanium tetrachloride (47 mg, 0.25 mmol) were added to 2-[2-(2,5-dimethylphenoxymethyl)-phenyl]-2-methoxyiminoacetamide (1.56 g, 5 mmol, E/Z=9/91). The mixture was stirred at 80°C for 24 hours. After completion of the reaction, water (50 ml) was added. The resulting mixture was extracted with toluene (50 ml) twice, washed with 1N aqueous sodium hydroxide solution, water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give pale green crystals (1.56 g)(Yield: 100%, E/Z=97/3). (4) Toluene (5 ml), titanium tetrachloride (47 mg, 0.25 mmol) and 5N hydrochloric acid (0.1 ml) were added to 2-[2-(2,5-dimethylphenoxymethyl)phenyl]-2-methoxyiminoacetamide (1.56 g, 5 mmol, E/Z=9/91). The mixture was stirred at 80°C for 2 hours. After completion of the reaction, water (50 ml) was added. The resulting mixture was extracted with toluene (50 ml) twice, washed with 1N aqueous sodium hydroxide solution, water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give pale brown crystals (1.55 g)(Yield: 99%, E/Z=97/3). Example 13 Synthesis of (E)-2-(2-chloro-3-pyridyloxymethyl)-a-methoxyiminophenylacetic acid Methanol (2 ml) and a 50% aqueous solution of potassium hydroxide (0.07 g, 0.66 mmol) were added to (E)-2-(2-chloro-3-pyridyloxymethyl)-α-methoxyiminophenylacetonitrile (0.11 g, 0.33 mmol). The mixture was stirred under reflux for 6 hours. After completion of the reaction, water (100 ml) was added, and the resulting mixture was washed with methylene chloride (50 ml). Hydrochloric acid (1N, 1 ml) was added, and the mixture was extracted with methylene chloride (50 ml) twice. The methylene chloride layer was dried over anhydrous magnesium sulfate and evaporated under reduced pressure to dryness to give (E)-2-(2-chloro-3-pyridyloxymethyl)-α-methoxyiminophenylacetic acid (0.05 g, 42.8 %) as colorless crystals. 1 H-NMR(CDCl 3 ) δ ppm: 4.21(3H,s), 5.11(2H,s), 7.11-7.52(6H,m), 7.98-8.00(1H,m). Example 14 Synthesis of (E)-2-[2-(2-chloro-3-pyridyloxymethyl)phenyl]-2-methoxyimino-N-methylacetamide 1,2-Dichloroethane (1 ml), thionyl chloride (0.03 g, 0.28 mmol) and dimethylformamide (DMF)(0.01 ml) were added to (E)-2-(2-chloro-3-pyridyloxymethyl)-α-methoxyiminophenylacetic acid (0.05 g, 0.14 mmol). The mixture was stirred under reflux for 1 hour. To the reaction mixture was added 40% methylamine/methanol solution (1 ml) under ice-cooling. The mixture was stirred at 0°C for 1 hour. After completion of the reaction, water (100 ml) was added, and the mixture was extracted with methylene chloride (50 ml) twice. The methylene chloride layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give (E)-2-[2-(2-chloro-3-pyridyloxymethyl)phenyl]-2-methoxyimino-N-methylacetamide (0.02 g, 42.8 %) as colorless crystals. A part of them was recrystallized from ethyl acetate/n-hexane to give crystals (mp. 128-129°C). 1 H-NMR(CDCl 3 ) δ ppm: 2.90(3H,d,J=5.5), 3.94 (3H,s), 5.10(2H,s), 6.84(1H,brs), 7.11-7.53(6H,m), 7.95-7.97(1H,m).

Claims: A process for producing an alkoxyiminoacetamide compound of the formula (I): wherein A is hydrogen, C 1 -C 8 alkyl, C 2 -C 8 alkenyl, C 2 -C 8 alkynyl, C 1 -C 8 alkoxy, cyclo(C 3 -C 8 )alkyl, cyclo(C 3 -C 8 )-alkenyl, optionally substituted phenyl or an optionally substituted heterocyclic group; B is -CH 2 -, -O-, -S-, -CH(OH)-, -CO-, -NR 3 - (wherein R 3 is hydrogen or C 1 -C 8 alkyl), -CH 2 CH 2 -, -CH=CH-, -C≡C-, -CH 2 O-, -CH 2 S-, -CH 2 S(O) -, -OCH 2 -, -SCH 2 -, -S(O)CH 2 - or epoxy; R is C 1 -C 8 alkyl; and R 1 and R 2 are each independently hydrogen or C 1 -C 8 alkyl; which process comprises halogenating a compound of the formula (III): wherein the bond ∼ represents any configuration of the E-isomer, Z-isomer or a mixture of the E- and Z-isomers and the other symbols are as defined above, to obtain a compound of the formula (IV): wherein X is halogen and the other symbols are as defined above; reacting the compound of the formula (IV) with an amine of the formula: HNR 1 R 2 (wherein R 1 and R 2 are as defined above); and treating the resulting compound with an acid for isomerisation to increase the E-isomer content, wherein said halogenation is carried out by the addition of a halogenating agent to said compound of formula III over a period of time between 5 and 24 hours. A process according to claim 1, wherein the compound of the formula (III) is obtained by reacting a compound of the formula (II): wherein each symbol is as defined in claim 1, with a base. A process according to any preceding claim, wherein A is optionally substituted phenyl. A process according to claim 3, wherein A is unsubstituted phenyl. A process according to claim 3, wherein A is phenyl substituted with C 1 -C 8 alkyl and/or halogen. A process according to claim 5, wherein A is phenyl substituted with mono- or dimethyl and/or chlorine or fluorine. A process according to claim 6, wherein A is 2,5-dimethylphenyl, 4-fluorophenyl, 4-chlorophenyl, 3,4-dimethylphenyl, 2-methylphenyl, 2-chlorophenyl, 2-methyl-4-chlorophenyl or 3,5-dimethylphenyl. A process according to any one of claims 1 or 2, wherein A is an optionally substituted heterocvclic group. A process according to claim 8, wherein A is optionally substituted pyridyl. A process according to claim 9, wherein A is pyridyl substituted with halogen and/or halogenated C 1 -C 8 alkyl. A process according claim 10, wherein A is pyridyl substituted with chlorine and/or trifluoromethyl. A process according to claim 11, wherein A is 5-trifluoromethylpyridyl, 5-chloro-3-trifluoromethylpyridyl or 6-chloro-3-trifluoromethylpyridyl. A process according to any preceding claim, wherein B is -O-, -CH 2 O- or -OCH 2 -. A process according to claim 1, wherein A is phenyl, 4-chlorophenyl, 4-fluorophenyl, 3,4-dimethylphenyl or 3,5-dimethylphenyl; B is -O-; R is methyl; R 1 is hydrogen; and R 2 is methyl. A process according to claim 1, wherein wherein A is 2-methylphenyl, 2-chlorophenyl, 4-chlorophenyl, 2,5-dimethylphenyl or 4-chloro-2-methylphenyl; B is -OCH 2 -; R is methyl; R 1 is hydrogen; and R 2 is methyl. A process according to claim 1, wherein A is 5-trifluoromethylpyridyl, 5-chloro-3-trifluoromethylpyridyl or 6-chloro-3-trifluoromethylpyridyl; B is -OCH 2 -; R is methyl; R 1 is hydrogen; and R 2 is methyl.

Inventors: IWAKAWA TSUNEO, KAI HIROYUKI, MASUI MORIYASU, TAKASE AKIRA, UEDA KAZUO, IWAKAWA, TSUNEO, KAI, HIROYUKI, MASUI, MORIYASU, TAKASE, AKIRA, UEDA, KAZUO
Applicants: SHIONOGI & CO, SHIONOGI & CO., LTD.
Application year: 1994
Main classification: C07C251
IPC codes: C07D213, C07C251, C07C249